Peptidomimetic inhibitors of PSMA, compounds comprising them, and methods of use

The compound or pharmaceutically acceptable salt thereof, of the formula,

• wherein
• each n is independently 1, 2, 3, 4, 5 or 6;
• each R1 and R2 are independently —C(O)OR3, —C(O)N(R3)2, —P(O)(OR3)2, —OP(O)(OR3)2, —S(O)2R3, —S(O)2OR3, —S(O)2N(R3)2, or tetrazolyl;
• each R3 is independently —H or C1-C6 alkyl;
• R4 is —H, —C(O)OR3, —C(O)N(R3)2, —P(O)(OR3)2, —OP(O)(OR3)2, —S(O)2R3, —S(O)2OR3, —S(O)2N(R3)2, or tetrazolyl;
• L is —P(O)(OR3)—, or —P(O)(N(R3)2)—;
• M and T are independently —O—, —S—, —N(R3)—, or —CH2—;
• R10 is —H, —C1-C6 alkyl, aryl, —C1-C6 alkyl-aryl, -aryl-aryl, —X—R6, —R7, —C(O)R5, —S(O)2R5, peptide, dendrimer, or peptide dendrimer, wherein
• X is —O—, —S—, or —N(R3)—;
• R5 is —CH(R51)N(R52)2;
• C1-C6 alkyl optionally substituted with 1 to 3 groups which are independently -halogen, COOR53, or —N(R52)2;
• aryl;
• or heteroaryl, wherein
• R51 is —H, aryl, heteroaryl, C1-C6 alkyl-aryl optionally substituted with —OH;
• C1-C6 alkyl-heteroaryl, or C1-C6 alkyl optionally substituted with —OR53, —SR53, —NH2, —N(H)C(═NH)NH2, —COOR53, or —C(O)N(R53)2;
• and
• R52 is —H, C1-C6alkyl, —C(O)R53, C(O)OR53, —C(O)NH(C1-C6alkyl), —C(O)N(R53)2, —C(O)aryl, or —C(O)heteroaryl;
• R53 is —H, C1-C6alkyl, or C1-C6 alkyl-aryl;
• R6 is —H or C1-C6 alkyl;
• and
• R7 is —L1—R8, wherein
• L1 is —C(O)N(R3)—, —C(S)N(R3)—, —C(O)CH(R21)—, —C(O)(O), or —C(O)—L2—,
• wherein
• R21 is —H, aryl, heteroaryl, C1-C6 alkyl-aryl optionally substituted with —OH;
• C1-C6 alkyl-heteroaryl, or C1-C6 alkyl optionally substituted with —OR23, —SR23, —NH2, —N(H)C(═NH)NH2, —COOR23, or —C(O)N(R23)2;
• and
• R23 is —H, C1-C6alkyl, or C1-C6 alkyl-aryl;
• L2 is —C1-C24 alkyl- or -phenyl-C1-C24 alkyl-, wherein
• each alkyl group is optionally substituted with 1 to 4 groups which are oxo, ═S, or —COOH;
• and
• one to six of the methylene groups in each alkyl group is optionally replaced by —O—, —S—, or —N(R3)—, provided that no two adjacent methylene groups are both replaced by —O—, —S—, or —N(R3)—;
• and
• R8 is —H, —NH2, or —OH;
• and
• Q is —O—, —S—, —N(R3)—, —N(R3)O—, —ON(R3)—, —CH2—, or ═NO—.